Progesterone
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225825786
2008-07-15T16:03:47Z
Boghog2
2428506
Reverted edits by [[Special:Contributions/192.35.79.70|192.35.79.70]] ([[User talk:192.35.79.70|talk]]) to last version by Lemccan
{{drugbox |
| IUPAC_name = pregn-4-ene-3,20-dione
| image = Progesterone-2D-skeletal.png
| image2 = Progesterone-3D-vdW.png
| width=200 <!-- low res image -->
| CAS_number = 57-83-0
| ATC_prefix = G03
| ATC_suffix =DA04
| PubChem = 5994
| DrugBank = APRD00700
| C=21 | H=30 | O=2
| molecular_weight = 314.47
| melting_point = 126
| specific_rotation = [α]<sub>D</sub>
| synonyms = 4-pregnene-3,20-dione
| bioavailability = prolonged absorption, half-life approx 25-50 hours
| protein_bound = 96%-99%
| metabolism = [[hepatic]] to pregnanediols and pregnanolones
| elimination_half-life = 34.8-55.13 hours
| excretion = renal
| pregnancy_category = B ([[United States|USA]])
| legal_status =
| routes_of_administration = oral, [[Implant (medicine)|implant]]
}}
'''Progesterone''' is a C-21 [[steroid]] [[hormone]] involved in the [[female]] [[menstrual cycle]], [[pregnancy]] (supports ''[[gestation]]'') and [[embryogenesis]] of humans and other species. Progesterone belongs to a class of hormones called [[progestogens]], and is the major naturally occurring human progestogen.
Progesterone should not be confused with [[progestins]], which are synthetically produced [[progestogens]].
==Chemistry==
Progesterone was independently discovered by four research groups.<ref name="pmid17747122">{{cite journal | author = Allen WM | title = The isolation of crystalline progestin | journal = Science | volume = 82 | issue = 2118 | pages = 89–93 | year = 1935 | pmid = 17747122 | doi = 10.1126/science.82.2118.89 }}</ref><ref name="Butenandt_1934">{{cite journal | author = Butenandt A, Westphal U | title = Zur Isolierung und Charakterisierung des Corpusluteum-Hormons | journal = Berichte Deutsche chemische Gesellschaft | volume = 67 | issue = | pages = 1440–1442 | year = 1934 | pmid = | doi = | issn = }}</ref><ref name="Hartmann_1934">{{cite journal | author = Hartmann M, Wettstein A | title = Ein krystallisiertes Hormon aus Corpus luteum | journal = Helvetica Chimica Acta | volume = 17 | issue = | pages = 878–882 | year = 1934| doi = 10.1002/hlca.193401701111 }}</ref><ref name="Slotta_1934">{{cite journal | author = Slotta KH, Ruschig H, Fels E | title = Reindarstellung der Hormone aus dem Corpusluteum | journal = Berichte Deutsche chemische Gesellschaft | volume = 67 | issue = | pages = 1270–1273 | year = 1934 | pmid = | doi = | issn = }}</ref>
[[Willard Myron Allen]] co-discovered progesterone with his anatomy professor George Washington Corner at the University of Rochester Medical School in 1933. Allen first determined its melting point, molecular weight, and partial molecular structure. He also gave it the name '''Progesterone''' derived from '''Proge'''stational '''Ster'''oidal ket'''one'''.<ref name="pmid4922128">{{cite journal | author = Allen WM | title = Progesterone: how did the name originate? | journal = South. Med. J. | volume = 63 | issue = 10 | pages = 1151–5 | year = 1970 | pmid = 4922128 | doi = | issn = }}</ref>
Like other [[steroid]]s, progesterone consists of four interconnected [[cyclic hydrocarbon]]s. Progesterone contains [[ketone]] and oxygenated functional groups, as well as two [[methyl]] branches. Like all steroid hormones, it is [[hydrophobic]].
===Synthesis===
Progesterone, like all other [[steroid]] [[hormone]]s, is synthesized from [[pregnenolone]], a derivative of [[cholesterol]]. This conversion takes place in two steps. The 3-[[hydroxyl]] group is converted to a [[ketone|keto]] group and the [[double bond]] is moved to C-4, from C-5.
[[Image:Reaction-Pregnenolone-Progesterone2.png|thumb|center|350px|Conversion of Pregnenolone to Progesterone]]
Progesterone is the precursor of the mineralocorticoid [[aldosterone]], and after conversion to [[17-hydroxyprogesterone]] (another natural progestogen) of [[cortisol]] and [[androstenedione]]. Androstenedione can be converted to [[testosterone]], [[estrone]] and [[estradiol]].
[[Image:DHEA1.svg|thumb|center|350px|Progesterone is important for [[aldosterone]] ([[mineralocorticoid]]) synthesis, as [[17-hydroxyprogesterone]] is for [[cortisol]] ([[glucocorticoid]]), and [[androstenedione]] for [[sex steroids]].]]
==Sources==
Progesterone is produced in the [[adrenal gland]]s, the gonads (specifically after ovulation in the [[corpus luteum]]), the brain, and, during pregnancy, in the [[placenta]].
In humans, increasing amounts of progesterone are produced during pregnancy:
* Initially, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropins ([[Human chorionic gonadotropin|hCG]]) from the conceptus.
* However, after the 8th week production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal [[corticosteroids]]. At term the placenta produces about 250 mg progesterone per day.
* An additional source of progesterone is milk products. They contain much progesterone because on dairy farms cows are milked during pregnancy, when the progesterone content of the milk is high. After consumption of milk products the level of bioavailable progesterone goes up.<ref name="titleResult Content View">{{cite web | url = http://www.abstracts2view.com/sabcs/view.php?nu=SABCS07L_1108&terms | title = Milk products are a source of dietary progesterone | accessdate = 2008-03-12 | author = Goodson III WH, Handagama P, Moore II DH, Dairkee S | authorlink = | coauthors = | date = 2007-12-13 | format = | work = | publisher = 30th Annual San Antonio Breast Cancer Symposium | pages = abstract # 2028 | language = | archiveurl = | archivedate = | quote = }}</ref> This observation has resulted in concern that diets high in dairy products might induce pet and human diseases.<ref name="titleBreast Cancer and Progesterone from the Milk of Pregnant Cows">{{cite web | url = http://www.erieping.de/english.htm | title = Breast Cancer and Progesterone from the Milk of Pregnant Cows | accessdate = 2008-03-12 | author = Elisabeth Rieping | authorlink = | coauthors = | date = 2008-01-01 | format = | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = }}</ref>
==Levels==
[[Image:Estradiol.Cycle.JPG|right|thumb|300 px|Progesterone levels (black line) during the menstrual cycle]]
In women, progesterone levels are relatively low during the preovulatory phase of the [[menstrual cycle]], rise after [[ovulation]], and are elevated during the luteal phase. Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If [[pregnancy]] occurs, progesterone levels are initially maintained at luteal levels. With the onset of the luteal-placental shift in progesterone support of the pregnancy, levels start to rise further and may reach 100-200 ng/ml at term. Whether a decrease in progesterone levels is critical for the initiation of [[labor (childbirth)|labor]] has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.
Progesterone levels are relatively low in children and postmenopausal women.<ref name="titleHistorical Reference Ranges">{{cite web | url = http://cclnprod.cc.nih.gov/dlm/testguide.nsf/Index/CB26894E1EB28DEF85256BA5005B000E?OpenDocument | title = Progesterone Historical Reference Ranges | accessdate = 2008-03-12 | author = NIH Clinical Center | authorlink = | coauthors = | date = 2004-08-16 | format = | work = | publisher = United States National Institutes of Health | pages = | language = | archiveurl = | archivedate = | quote = }}</ref> Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.
==Effects==
Progesterone exerts its action primarily through the intracellular [[progesterone receptor]] although a distinct, membrane bound progesterone receptor has also been postulated.<ref name="pmid9506743">{{cite journal | author = Luconi M, Bonaccorsi L, Maggi M, Pecchioli P, Krausz C, Forti G, Baldi E | title = Identification and characterization of functional nongenomic progesterone receptors on human sperm membrane | journal = J. Clin. Endocrinol. Metab. | volume = 83 | issue = 3 | pages = 877–85 | year = 1998 | pmid = 9506743 | doi = 10.1210/jc.83.3.877 }}</ref><ref name="pmid15684349">{{cite journal | author = Jang S, Yi LS | title = Identification of a 71 kDa protein as a putative non-genomic membrane progesterone receptor in boar spermatozoa | journal = J. Endocrinol. | volume = 184 | issue = 2 | pages = 417–25 | year = 2005 | pmid = 15684349 | doi = 10.1677/joe.1.05607 }}</ref> Progesterone has a number of physiological effects which are amplified in the presence of [[estrogen]]. Estrogen through estrogen receptors [[upregulation|upregulates]] the [[gene expression|expression]] of progesterone receptors. <ref name="pmid2328727">{{cite journal | author = Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P | title = Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B | journal = EMBO J. | volume = 9 | issue = 5 | pages = 1603–14 | year = 1990 | pmid = 2328727 | doi = | issn = }}</ref>
===Reproductive system===
Progesterone is sometimes called the "hormone of pregnancy",<ref name="colostate">{{cite web | url = http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/endocrine.html | title = Placental Hormones | accessdate = 2008-03-12 | author = Bowen R | authorlink = | coauthors = | date = 2000-08-06 | format = | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = }}</ref> and it has many roles relating to the development of the fetus:
* Progesterone converts the [[uterine lining|endometrium]] to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the vaginal [[epithelium]] and [[Cervix#Cervical_mucus|cervical mucus]], making the [[mucus]] thick and impermeable to [[sperm]]. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to [[menstruation]]. Normal menstrual bleeding is progesterone withdrawal bleeding.
* During implantation and [[gestation]], progesterone appears to decrease the maternal [[immune system|immune]] response to allow for the acceptance of the pregnancy.
* Progesterone decreases contractility of the uterine [[smooth muscle]].<ref name="colostate"/>
* In addition progesterone inhibits [[lactation]] during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
* A drop in progesterone levels is possibly one step that facilitates the onset of [[labor (childbirth)|labor]].
The [[fetus]] [[metabolize]]s placental progesterone in the production of [[adrenal]] mineralo- and glucosteroids.
===Nervous system===
Progesterone, like [[pregnenolone]] and [[dehydroepiandrosterone]], belongs to the group of [[neurosteroid]]s that are found in high concentrations in certain areas in the brain and are synthesized there.
[[neuroactive steroid|Neurosteroids]] affect [[synapse|synaptic functioning]], are neuroprotective, and affect [[myelin]]ization.<ref name="pmid15135772">{{cite journal | author = Schumacher M, Guennoun R, Robert F, ''et al'' | title = Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination | journal = Growth Horm. IGF Res. | volume = 14 Suppl A | issue = | pages = S18–33 | year = 2004 | pmid = 15135772 | doi = 10.1016/j.ghir.2004.03.007| accessdate = }}</ref> They are investigated for their potential to improve [[memory]] and [[cognition|cognitive ability]].
Progesterone as neuroprotectant affects regulation of [[apoptosis|apoptotic]] genes.
Its effect as a neurosteroid works predominantly through the [[GSK-3]] beta pathway, as an inhibitor. (Other GSK-3 beta inhibitors include [[bipolar disorder|bipolar]] mood stabilizers, [[lithium]] and [[valproic acid]].)
===Other systems===
* It raises [[epidermal growth factor-1]] levels, a factor often used to induce proliferation, and used to sustain cultures, of [[stem cell]]s.
* It increases core temperature (thermogenic function) during ovulation.<ref name="GeorgiaPhysiology">{{GeorgiaPhysiology|5/5ch9/s5ch9_13}}</ref>
* It reduces [[spasm]] and relaxes [[smooth muscle]]. [[Bronchi]] are widened and [[mucus]] regulated. ([[Progesterone receptor]]s are widely present in [[Mucous membrane|submucosal tissue]].)
* It acts as an [[Inflammation|antiinflammatory]] agent and regulates the [[immune response]].
* It reduces [[gall-bladder]] activity.<ref name="pmid3184927">{{cite journal | author = Hould FS, Fried GM, Fazekas AG, Tremblay S, Mersereau WA | title = Progesterone receptors regulate gallbladder motility | journal = J. Surg. Res. | volume = 45 | issue = 6 | pages = 505–12 | year = 1988 | pmid = 3184927| doi = 10.1016/0022-4804(88)90137-0 }}</ref>
* It normalizes [[blood]] clotting and vascular tone, [[zinc]] and [[copper]] levels, [[cell (biology)|cell]] [[oxygen]] levels, and use of fat stores for energy.
* It assists in [[thyroid]] function, in [[bone]] building by [[osteoblast]]s, in [[bone]], [[teeth]], [[gingiva|gum]]s, [[joint]], [[tendon]], [[ligament]] and [[skin]] [[resilience]] and in some cases healing by regulating various types of [[collagen]], and in nerve function and healing by regulating [[myelin]].
* It appears to prevent [[endometrial cancer]] (involving the uterine lining) by regulating the effects of estrogen.
==Medical applications==
The use of progesterone and its analogues have many medical applications -- both to address acute situations, and to address the long-term decline of natural progesterone levels. Because of the poor bioavailability of progesterone when taken orally, many synthetic progestins have been designed. However, the roles of progesterone may not be fulfilled by the synthetic progestins which in some cases were designed solely to [[mimic]] progesterone's [[Uterus|uterine]] effects.
===[[Bioavailability]]===
Progesterone is poorly absorbed by oral ingestion unless [[micronize|micronised]] and in oil, or with fatty foods; it does not dissolve in water. Products such as Prometrium, Utrogestan, Minagest and Microgest are therefore capsules containing micronised progesterone in oil - in all three mentioned the oil is [[peanut]] oil, which may cause serious [[allergic reactions]] in some people, but compounding [[pharmacies]], which have the facilities and licenses to make their own products, can use alternatives. Vaginal and rectal application is also effective, with products such as CRINONE and PROCHIEVE bioadhesive progesterone vaginal gels (the only progesterone products FDA-approved for use in infertility and during pregnancy) and Cyclogest, which is progesterone in [[cocoa butter]] in the form of [[Pessary|pessaries]]. Progesterone can be given by [[Injection (medicine)|injection]], but because it has a short [[Exponential decay|half-life]] they need to be daily. Implants, for a longer period, are also available. Marketing of progesterone phamaceutical products, country to country, varies considerably, with many countries having no oral progesterone products marketed, but they can usually be specially imported by pharmacies through international [[wholesaler]]s.
"Natural progesterone" products derived from [[yam (vegetable)|yams]], do not require a prescription. Wild yams contain a [[plant steroid]] called [[diosgenin]], however there is no evidence that the human body can [[metabolize]] diosgenin into progesterone.<ref name="pmid9492350">{{cite journal | author = Zava DT, Dollbaum CM, Blen M | title = Estrogen and progestin bioactivity of foods, herbs, and spices | journal = Proc. Soc. Exp. Biol. Med. | volume = 217 | issue = 3 | pages = 369–78 | year = 1998 | pmid = 9492350 | doi = | issn = | url = http://www.cancersupportivecare.com/estrogenherbref.html#31 }}</ref><ref name="pmid11428178">{{cite journal | author = Komesaroff PA, Black CV, Cable V, Sudhir K | title = Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women | journal = Climacteric | volume = 4 | issue = 2 | pages = 144–50 | year = 2001 | pmid = 11428178| doi = 10.1080/713605087 }}</ref> Diosgenin can however be chemically converted into progesterone in the lab.<ref name="Marker_1940">{{cite journal | author = Marker RE, Krueger J | title = Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone | journal = J. Am. Chem. Soc. | volume = 62 | issue = 12 | pages = 3349–3350 | year = 1940| doi = 10.1021/ja01869a023 }}</ref>
===Specific uses===
*Progesterone is used to support pregnancy in Assisted Reproductive Technology (ART) cycles such as In-vitro Fertilization (IVF). While daily intramuscular injections of progesterone have been the standard route of administration, a recent meta-analysis showed that the intravaginal route with an appropriate dose and dosing frequency is equivalent to daily intramuscular injections.<ref name="Zarutskiea_2007">{{cite journal | author = Zarutskiea PW, Phillips JA | title = Re-analysis of vaginal progesterone as luteal phase support (LPS) in assisted reproduction (ART) cycles | journal = Fertility and Sterility | volume = 88 | issue = supplement 1 | pages = S113 | year = 2007| doi = 10.1016/j.fertnstert.2007.07.365 }}</ref>
*Progesterone is used to control [[anovulatory bleeding]]. It is also used to prepare uterine lining in [[infertility]] therapy and to support early pregnancy. Patients with [[habitual abortion|recurrent pregnancy loss]] due to inadequate progesterone production may receive progesterone.
* Progesterone is being investigated as potentially beneficial in treating [[multiple sclerosis]], since the characteristic deterioration of nerve [[myelin]] insulation halts during pregnancy, when progesterone levels are raised; deterioration commences again when the levels drop.
*Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. The initial study by Fonseca suggested that vaginal progesterone could prevent preterm birth in women with a history of preterm birth.<ref name="pmid12592250">{{cite journal | author = da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M | title = Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study | journal = Am. J. Obstet. Gynecol. | volume = 188 | issue = 2 | pages = 419–24 | year = 2003 | pmid = 12592250 | doi = 10.1067/mob.2003.41 }}</ref>
A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth,<ref name="pmid17899572">{{cite journal | author = O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW | title = Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial | journal = Ultrasound Obstet Gynecol | volume = 30 | issue = 5 | pages = 687–96 | year = 2007 | pmid = 17899572 | doi = 10.1002/uog.5158 }}</ref> but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care.<ref name="pmid17899571">{{cite journal | author = DeFranco EA, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, Soma-Pillay P, Porter K, How H, Schakis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW | title = Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial | journal = Ultrasound Obstet Gynecol | volume = 30 | issue = 5 | pages = 697–705 | year = 2007 | pmid = 17899571 | doi = 10.1002/uog.5159 }}</ref> In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline.<ref name="pmid17671254">{{cite journal | author = Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH | title = Progesterone and the risk of preterm birth among women with a short cervix | journal = N. Engl. J. Med. | volume = 357 | issue = 5 | pages = 462–9 | year = 2007 | pmid = 17671254 | doi = 10.1056/NEJMoa067815 }}</ref> An editorial by Roberto Romero discusses the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment.<ref name="pmid17899585">{{cite journal | author = Romero R | title = Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment | journal = Ultrasound Obstet Gynecol | volume = 30 | issue = 5 | pages = 675–86 | year = 2007 | pmid = 17899585 | doi = 10.1002/uog.5174 }}</ref>
* Progesterone is used in [[Hormone replacement therapy (male-to-female)|hormone replacement therapy]] for [[transwomen]], and some women with [[intersex]] conditions - especially when synthetic progestins have been ineffective or caused side-effects - since normal [[breast]] tissue cannot develop except in the presence of both progestogen and [[estrogen]]. [[Mammary gland]]ular tissue is otherwise [[fibrosis|fibrotic]], the breast shape [[cone (geometry)|conical]] and the [[areola]] immature. Progesterone can correct those even after years of inadequate hormonal treatment. Research usually cited against such value was conducted using Provera, a synthetic progestin. Progesterone also has a role in skin elasticity and bone strength, in [[Respiration (physiology)|respiration]], in nerve tissue and in [[female sexuality]], and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in [[Sexual dimorphism|sexually-dimorphic]] proportions of those.
* Progesterone [[receptor antagonist]]s, or [[selective progesterone receptor modulator]]s (SPRM)s, such as [[RU-486]] ([[Mifepristone]]), can be used to prevent conception or induce [[medical abortion]]s.
Note that methods of [[hormonal contraception]] do not contain progesterone but a [[progestin]].
Progesterone may affect male behavior.<ref name="pmid12601162">{{cite journal | author = Schneider JS, Stone MK, Wynne-Edwards KE, Horton TH, Lydon J, O'Malley B, Levine JE | title = Progesterone receptors mediate male aggression toward infants | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 5 | pages = 2951–6 | year = 2003 | pmid = 12601162 | doi = 10.1073/pnas.0130100100 }}</ref>
Lawn chemicals and no-till agricultual practices may disturb both estrogen and progesterone metabolism. {{Fact|date=March 2008}}
===Aging===
Since most progesterone in males is created during testicular production of [[testosterone]], and most in females by the [[ovaries]], the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of [[progestagen]]s (progesterone and molecules with similar effects) in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.
The tendency for progesterone to have a regulatory effect, the presence of progesterone [[receptor (biochemistry)|receptor]]s in many types of body tissue, and the pattern of deterioration (or [[tumor]] formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.
===Brain damage===
It has been observed in animal models that females have reduced susceptibility to [[traumatic brain injury]] and this protective effect has been hypothesized to be caused by increased circulating levels of [[estrogen]] and progesterone in females.<ref name="pmid10833057">{{cite journal | author = Roof RL, Hall ED | title = Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone | journal = J. Neurotrauma | volume = 17 | issue = 5 | pages = 367–88 | year = 2000 | month = May | pmid = 10833057 | doi = | url = | issn = }}</ref> A number of additional animal studies have confirmed that progesterone has neuroprotective effects when administered shortly after traumatic brain injury.<ref name="pmid17715141">{{cite journal | author = Gibson CL, Gray LJ, Bath PM, Murphy SP | title = Progesterone for the treatment of experimental brain injury; a systematic review | journal = Brain | volume = 131 | issue = Pt 2 | pages = 318–28 | year = 2008 | month = February | pmid = 17715141 | doi = 10.1093/brain/awm183 | url = }}</ref> Encouraging results have also been reported in human clinical trials.<ref name="pmid17011666">{{cite journal | author = Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG | title = ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury | journal = Ann Emerg Med | volume = 49 | issue = 4 | pages = 391–402, 402.e1–2 | year = 2007 | month = April | pmid = 17011666 | doi = 10.1016/j.annemergmed.2006.07.932 | url = }}</ref><ref name="pmid18447940">{{cite journal | author = Xiao G, Wei J, Yan W, Wang W, Lu Z | title = Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial | journal = Crit Care | volume = 12 | issue = 2 | pages = R61 | year = 2008 | month = April | pmid = 18447940 | doi = 10.1186/cc6887 | url = }}</ref>
The mechanism of progesterone protective effects may be the reduction of inflammation which follows brain trauma.<ref name="pmid18188998">{{cite journal | author = Pan DS, Liu WG, Yang XF, Cao F | title = Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury | journal = Biomed. Environ. Sci. | volume = 20 | issue = 5 | pages = 432–8 | year = 2007 | month = October | pmid = 18188998 | doi = | url = | issn = }}</ref>
==See also==
*[[Willard Myron Allen]]
*[[Bioidentical hormone replacement therapy]]
*[[Prometrium]]
==References==
{{Reflist|2}}
==Additional images==
<gallery>
Image:Steroidogenesis.gif|[[Steroidogenesis]]
Image:Pregnenolone.png|[[Pregnenolone]]
Image:Deoxycorticosterone.svg|[[Deoxycorticosterone]]
</gallery>
==External links==
* {{MeshName|Progesterone}}
* {{cite web | url = http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Progesterone.html | title = Progesterone | author = Kimball JW | authorlink = | coauthors = | date = 2007-05-27 | format = | work = Kimball's Biology Pages | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-06-18 }}
* {{cite web | url = http://www.pms-menopause-progesterone.org/progesterone/ | title = Progesterone Resource Center | author = | authorlink = | coauthors = | date = | format = | work = PMS, Menopause, and Progesterone Resource Center | publisher = Oasis Advanced Wellness, Inc | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-06-18}}
{{Hormones}}
{{Sex hormones}}
[[Category:Progestagens]]
[[Category:Neurosteroids]]
[[bg:Прогестерон]]
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